The clinical utility of molecular karyotyping for neurocognitive phenotypes in a consanguineous population
The clinical utility of molecular karyotyping for neurocognitive phenotypes in a consanguineous population
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DOI：
10.1038/gim.2014.184
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发表时间：
2015-09-01
影响因子：
8.8
通讯作者：
Alkuraya, Fowzan S.
中科院分区：
文献类型：
--
作者：
Al-Qattan, Sarah M.;Wakil, Salma M.;Alkuraya, Fowzan S.
目的：分子核型分析已迅速成为神经认知表型患者的首选测试，但其临床应用的研究在很大程度上仅限于远交人群。在近亲人群中，神经认知表型的单基因隐性原因预计占相对较高的比例的情况下，从而减少了分子核型分析的产量。本研究的目的是测试的临床产量的分子核型分析在沙特阿拉伯的高度近亲人口。方法：我们已经审查了584例患者的数据与神经认知表型（主要是指从儿科神经科诊所），所有评估由一个单一的临床geneticist.Results：至少有21%的测试的情况下，染色体畸变是可能致病。这些变化包括已知的和新的缺失综合征。本研究中分子核型分析的产率高于通常引用的11%，这可以解释为我们能够有效地识别单基因疾病，从而丰富了进行从头染色体畸变分子核型分析的样本。我们表明，我们能够确定一个因果突变的37%的情况下，在临床基础上的帮助下，自体染色体组分析，从而绕过需要分子核型分析。结论：我们的研究证实了分子核型分析的临床实用性，即使在高度血缘关系的人群。
Purpose: Molecular karyotyping has rapidly become the test of choice in patients with neurocognitive phenotypes, but studies of its clinical utility have largely been limited to outbred populations. In consanguineous populations, single-gene recessive causes of neurocognitive phenotypes are expected to account for a relatively high percentage of cases, thus diminishing the yield of molecular karyotyping. The aim of this study was to test the clinical yield of molecular karyotyping in the highly consanguineous population of Saudi Arabia.Methods: We have reviewed the data of 584 patients with neurocognitive phenotypes (mainly referred from pediatric neurology clinics), all evaluated by a single clinical geneticist.Results: At least 21% of tested cases had chromosomal aberrations that are likely disease-causing. These changes include both known and novel deletion syndromes. The higher yield of molecular karyotyping in this study as compared with the commonly cited 11% can be explained by our ability to efficiently identify single-gene disorders, thus enriching the samples that underwent molecular karyotyping for de novo chromosomal aberrations. We show that we were able to identify a causal mutation in 37% of cases on a clinical basis with the help of autozygome analysis, thus bypassing the need for molecular karyotyping.Conclusion: Our study confirms the clinical utility of molecular karyotyping even in highly consanguineous populations.